Asymmetric Hydrolytic Kinetic Resolution with Recyclable Macrocyclic Co III –Salen Complexes: A Practical Strategy in the Preparation of ( R )‐Mexiletine and ( S )‐Propranolol

A chiral cobalt(III) complex ( 1 e ) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1 R ,2 R ‐(−)‐1,2‐diaminocyclohexane with trigol bis‐aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1 e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47 % with respect to the epoxides, 53 % with respect to the diols) and high enantioselectivity ( ee >99 % for the epoxides, up to 96 % for the diols) were achieved in 2.5–16 h. The Co III macrocyclic salen complex ( 1 e ) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules ( R )‐mexiletine and ( S )‐propranolol.